CN109232416A - A method of synthesis 4- trifluoromethyl -2- pyranone/pyridinone compounds - Google Patents

A method of synthesis 4- trifluoromethyl -2- pyranone/pyridinone compounds Download PDF

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CN109232416A
CN109232416A CN201811242838.6A CN201811242838A CN109232416A CN 109232416 A CN109232416 A CN 109232416A CN 201811242838 A CN201811242838 A CN 201811242838A CN 109232416 A CN109232416 A CN 109232416A
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trifluoromethyl
hydroresorcinol
pyranone
mmol
solvent
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CN109232416B (en
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翁志强
闫玮涛
吴伟
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Fuzhou University
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Fuzhou University
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D215/20—Oxygen atoms
    • C07D215/22—Oxygen atoms attached in position 2 or 4
    • C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D311/00—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings
    • C07D311/02—Heterocyclic compounds containing six-membered rings having one oxygen atom as the only hetero atom, condensed with other rings ortho- or peri-condensed with carbocyclic rings or ring systems
    • C07D311/04—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring
    • C07D311/06—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2
    • C07D311/20—Benzo[b]pyrans, not hydrogenated in the carbocyclic ring with oxygen or sulfur atoms directly attached in position 2 hydrogenated in the hetero ring
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B2200/00—Indexing scheme relating to specific properties of organic compounds
    • C07B2200/13—Crystalline forms, e.g. polymorphs

Abstract

The invention belongs to organic fluorine chemistries to synthesize field, and in particular to a method of synthesis 4- trifluoromethyl -2- pyrans/pyridinone compounds.Using organic base small molecule as catalyst, with 1, hydroresorcinol and the like, and trifluoroacetic ethyl acetoacetate or ammonium acetate are raw material, 1, it in 2- dichloroethane solvent, is stirred at 120-140 DEG C 16-48 hours, handles to obtain 4- trifluoromethyl -2- pyranone/pyridinone compounds after reaction through column chromatographic purifying.Synthetic method of the invention using non-metallic catalyst and catalyst is inexpensive, be easy to get, yield is generally higher, easy to operate the advantages that, have a good application prospect.

Description

A method of synthesis 4- trifluoromethyl -2- pyranone/pyridinone compounds
Technical field
The invention belongs to organic fluorine chemistries to synthesize field, and in particular to a kind of synthesis 4- trifluoromethyl -2- pyrans/pyridone The method of compound.
Background technique
2- pyranone compounds and its derivative are a kind of important heterocyclic compounds, specifically extensive bioactivity, such as Antimycotic, antibiotic, cytotoxicity, neurotoxicity and phytotoxicity.2- pyranone is also a kind of important chemical intermediate, is used In many drug molecules of synthesis.It, will be fluorine-containing since fluorine atom has mimic effect, electronic effect, stopping effect and osmotic effect Group is introduced on pyranone compounds and its derivative, it is possible to be enhanced its bioactivity, be shown different with non-fluorine molecule The characteristics of.The method of synthesis 4- trifluoromethyl -2- pyranone reported in the literature is less at present, needs multistep reaction, raw material is not easy ?.
The present invention provides a kind of synthesis 4- trifluoromethyl -2- pyranone/pyridone methods of simplicity, i.e., using organic Alkali small molecule prepares a series of 4- trifluoromethyl -2- pyranone/pyridine by the reaction of Pechmann type for catalyst Ketone compound.The method has many advantages, such as that raw material is simple, is easy to get, and catalyst is cheap.
Summary of the invention
The purpose of the present invention is to provide a kind of synthesis 4- trifluoromethyl -2- pyranone/pyridinone compounds methods, should Method is cheap and easy to get using non-metallic catalyst and raw material, and yield is generally higher, easy to operate, has a good application prospect.
To achieve the above object, the present invention adopts the following technical scheme:
A method of synthesis 4- trifluoromethyl -2- pyranone/pyridinone compounds, specifically: with organic base small molecule be urge Agent, with 1, hydroresorcinol and the like, trifluoroacetic ethyl acetoacetate or ammonium acetate are raw material, in a solvent, reaction system 4- trifluoromethyl -2- pyranone/pyridinone compounds are obtained, reaction process schematic diagram is as shown in Figure 1；The 4- trifluoromethyl- The structural formula of 2- pyranone compounds are as follows:；The knot of the 4- trifluoromethyl -2- pyridinone compounds Structure formula are as follows:。
The organic base micromolecule catalyst be 2- dimethylamino naphthyridine, 4-dimethylaminopyridine, triethylamine, pyridine and Any one of nafoxidine.
The solvent be 1,2- dichloroethanes, diethylene glycol dimethyl ether, dimethyl sulfoxide, N,N-dimethylformamide, Any one of nitrobenzene, N-Methyl pyrrolidone.
Described 1, hydroresorcinol and the like are any one of following structural formula 1- formula 7, as shown in Figure 2.It closes At the method for 4- trifluoromethyl -2- pyranone compounds, it is preferred that organic base micromolecule catalyst, 1, hydroresorcinol and its The molar ratio of analog, trifluoroacetic ethyl acetoacetate and solvent is 0.06-0.2:0.3-1:0.45-1.5:12.7-42.
The method for synthesizing 4- trifluoromethyl -2- pyridinone compounds, it is preferred that organic base micromolecule catalyst, 1,3- ring Acetyl butyryl and the like, trifluoroacetic ethyl acetoacetate, ammonium acetate and solvent molar ratio be 0.06-0.2:0.3-1: 0.45-1.5:0.9-3:12.7-42。
The method for synthesizing 4- trifluoromethyl -2- pyranone compounds, the specific steps are as follows: in nitrogen atmosphere, to having Organic base micromolecule catalyst, hydroresorcinol and the like, trifluoroacetyl second are added in the container of magnetic stirring apparatus Acetoacetic ester and solvent, shut plug after mixing, place it at 120 DEG C after continuing stirring 16 hours, with 100-200 mesh Silica gel filtering, methylene chloride rinse, and merge organic phase, are extracted with saturated ammonium chloride solution and ethyl acetate, and then revolving removes Organic solvent；Obtained crude product obtains 4- fluoroform using pentane and methylene chloride as eluant, eluent by silica gel column chromatography Base -2- pyranone compounds.
The method for synthesizing 4- trifluoromethyl -2- pyridinone compounds, the specific steps are as follows: in nitrogen atmosphere, to having Organic base micromolecule catalyst, hydroresorcinol and the like, trifluoroacetyl second are added in the container of magnetic stirring apparatus Acetoacetic ester, ammonium acetate and solvent, shut plug after mixing, place it at 140 DEG C after continuing stirring 48 hours, use The filtering of 100-200 mesh silica gel, methylene chloride rinse, and merge organic phase, are extracted with saturated sodium chloride solution and ethyl acetate, then Revolving removes organic solvent；Obtained crude product obtains 4- using pentane and ethyl acetate as eluant, eluent by silica gel column chromatography Trifluoromethyl -2- pyridinone compounds.
The beneficial effects of the present invention are:
For the present invention with 1, hydroresorcinol and the like is substrate, using trifluoroacetic ethyl acetoacetate or ammonium acetate as raw material, with Organic base small molecule is catalyst, and one pot process 4- trifluoromethyl -2- pyranone/pyridinone compounds obtains universal higher Yield, it is easy to operate, have a good application prospect.
Detailed description of the invention
Fig. 1 is that the present invention prepares 4- trifluoromethyl -2- pyranone/pyridinone compounds reacting flow chart；
Fig. 2 is the structural formula 1- formula 7 of hydroresorcinol and the like；
Fig. 3 is 4- (trifluoromethyl) -7,8- dihydro -2 made from embodiment 1HChromene -2,5 (6HThe monocrystalline knot of)-diketone Composition；
Fig. 4 is 7- phenyl -4- (trifluoromethyl) -7,8- dihydroquinoline -2,5 (1 made from embodiment 18H, 6HThe monocrystalline of)-diketone Structure chart.
Specific embodiment
In order to make content of the present invention easily facilitate understanding, With reference to embodiment to of the present invention Technical solution is described further, but the present invention is not limited only to this.
Embodiment 1
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1, hydroresorcinol, 1.0 mL 1,2- dichloroethanes, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 mmol trifluoroacetyl Ethyl acetate is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, merges organic phase, with full It being extracted with ammonium chloride solution and ethyl acetate, revolving removes organic solvent and obtains crude product, and crude product passes through silica gel column chromatography, with Pentane and dichloromethane eluent obtain 4- (trifluoromethyl) -7,8- dihydro -2HChromene -2,5 (6H(the separation of)-diketone Yield 99%).1H NMR (400 MHz, CDCl3) δ 6.67 (s, 1H), 2.94 (t, J = 6.2 Hz, 2H), 2.62 (t, J = 6.3 Hz, 2H), 2.17 (dt, J = 12.0 Hz, J = 6.2 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -63.6 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 190.8 (s), 176.2 (d, J = 1.3 Hz), 158.0 (s), 141.6 (q, J = 35.1 Hz), 120.8 (q, J = 275.1 Hz), 115.0 (q, J = 7.3 Hz), 111.3 (s), 38.0 (s), 29.2 (s), 19.4 (s).
Embodiment 2
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1, hydroresorcinol, 1.0 mL diethylene glycol dimethyl ethers, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 mmol trifluoro second Ethyl acetoacetic acid ethyl ester is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, and methylene chloride rinses, Merge organic phase, extracted with saturated ammonium chloride solution and ethyl acetate, then revolving removes organic solvent；Obtained crude product is logical Silica gel column chromatography is crossed, using pentane and methylene chloride as eluant, eluent, using trifluomethoxybenzene as internal standard, measures 4- (fluoroform Base) -7,8- dihydro -2HChromene -2,5 (6H)-diketone fluorine composes yield 66%.Nuclear magnetic spectrogram is shown in embodiment 1.
Embodiment 3
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1, hydroresorcinol, 1.0 mL nitrobenzenes, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 mmol trifluoroacetyl acetic acid second Ester is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, and methylene chloride rinses, and is merged organic Phase is extracted with saturated ammonium chloride solution and ethyl acetate, and then revolving removes organic solvent；Obtained crude product passes through silicagel column Chromatography, using pentane and methylene chloride as eluant, eluent, using trifluomethoxybenzene as internal standard, measures 4- (trifluoromethyl) -7,8- bis- Hydrogen -2HChromene -2,5 (6H)-diketone fluorine composes yield 73%.Nuclear magnetic spectrogram is shown in embodiment 1.
Embodiment 4
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1, hydroresorcinol, 1.0 mL n,N-Dimethylformamide, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 mmol trifluoro Ethyl acetoacetate is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, methylene chloride punching It washes, merges organic phase, extracted with saturated ammonium chloride solution and ethyl acetate, then revolving removes organic solvent；Obtained thick production Object, using trifluomethoxybenzene as internal standard, measures 4- (trifluoro using pentane and methylene chloride as eluant, eluent by silica gel column chromatography Methyl) -7,8- dihydro -2HChromene -2,5 (6H)-diketone fluorine composes yield 53%.Nuclear magnetic spectrogram is shown in embodiment 1.
Embodiment 5
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1, hydroresorcinol, 1.0 mL 1,2- dichloroethanes, 0.060 mmol pyridine, 0.45 mmol trifluoroacetic ethyl acetoacetate, oil It is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of bath, methylene chloride rinses, and merges organic phase, uses Saturated ammonium chloride solution and ethyl acetate extract, and then revolving removes organic solvent；Obtained crude product passes through silica gel column chromatography, Using pentane and methylene chloride as eluant, eluent, using trifluomethoxybenzene as internal standard, 4- (trifluoromethyl) -7,8- dihydro -2 is measuredH- Chromene -2,5 (6H)-diketone fluorine composes yield 64%.Nuclear magnetic spectrogram is shown in embodiment 1.
Embodiment 6
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1, hydroresorcinol, 1.0 mL 1,2- dichloroethanes, 0.060 mmol 4-dimethylaminopyridine, 0.45 mmol trifluoroacetyl Ethyl acetate is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, and methylene chloride rinses, and is closed And organic phase, it is extracted with saturated ammonium chloride solution and ethyl acetate, then revolving removes organic solvent；Obtained crude product passes through Silica gel column chromatography, using trifluomethoxybenzene as internal standard, measures 4- (trifluoromethyl)-using pentane and methylene chloride as eluant, eluent 7,8- dihydro -2HChromene -2,5 (6H)-diketone fluorine composes yield 55%.Nuclear magnetic spectrogram is shown in embodiment 1.
Embodiment 7
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1, hydroresorcinol, 1.0 mL 1,2- dichloroethanes, 0.060 mmol glutamic acid, 0.45 mmol trifluoroacetic ethyl acetoacetate, It being cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, methylene chloride rinses, merge organic phase, It is extracted with saturated ammonium chloride solution and ethyl acetate, then revolving removes organic solvent；Obtained crude product passes through silica gel column layer Analysis, using pentane and methylene chloride as eluant, eluent, using trifluomethoxybenzene as internal standard, measures 4- (trifluoromethyl) -7,8- dihydro - 2HChromene -2,5 (6H)-diketone fluorine composes yield 29%.Nuclear magnetic spectrogram is shown in embodiment 1.
Embodiment 8
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 5,5 '-dimethyl -1, hydroresorcinol, 1.0 mL 1,2- dichloroethanes, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 Mmol trifluoroacetic ethyl acetoacetate is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, is merged Organic phase is extracted with saturated ammonium chloride solution and ethyl acetate, and revolving removes organic solvent and obtains crude product, and crude product passes through silicon Plastic column chromatography obtains 7,7 '-dimethyl -4- (trifluoromethyl) -7,8- dihydro -2 with pentane and dichloromethane eluentHBenzo Pyrans -2,5 (6H)-diketone (separation yield 99%).1H NMR (400 MHz, CDCl3) δ 6.63 (s, 1H), 2.78 (s, 2H), 2.47 (s, 2H), 1.14 (s, 6H). 19F NMR (376 MHz, CDCl3) δ -63.6 (s, 3F).13C NMR (101 MHz, CDCl3) δ 190.8 (s), 174.7 (s), 158.3 (s), 141.4 (q, J = 35.4 Hz), 120.8 (q, J = 275.1 Hz), 114.8 (q, J = 7.4 Hz), 110.4 (s), 51.9 (s), 42.7 (s), 31.7 (s), 27.9 (s).
Embodiment 9
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 5,5 '-dimethyl -1, hydroresorcinol, 1.0 mL nitrobenzenes, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 mmol tri- Acetyl fluoride ethyl acetate is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, is merged organic Phase is extracted with saturated ammonium chloride solution and ethyl acetate, and revolving removes organic solvent and obtains crude product, and crude product passes through silicagel column Chromatography, with pentane and dichloromethane eluent, using trifluomethoxybenzene as internal standard, measures 7,7 '-dimethyl -4- (fluoroforms Base) -7,8- dihydro -2HChromene -2,5 (6H)-diketone fluorine composes yield 75%.Nuclear magnetic spectrogram is shown in embodiment 8.
Embodiment 10
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 5,5 '-dimethyl -1, hydroresorcinol, 1.0 mL diethylene glycol dimethyl ethers, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 Mmol trifluoroacetic ethyl acetoacetate is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, is merged Organic phase is extracted with saturated ammonium chloride solution and ethyl acetate, and revolving removes organic solvent and obtains crude product, and crude product passes through silicon Plastic column chromatography, using trifluomethoxybenzene as internal standard, measures 7,7 '-dimethyl -4- (trifluoros with pentane and dichloromethane eluent Methyl) -7,8- dihydro -2HChromene -2,5 (6H)-diketone fluorine composes yield 87%.Nuclear magnetic spectrogram is shown in embodiment 8.
Embodiment 11
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 2HPyrans -3,5 (4H,6H)-diketone, 1.0 mL 1,2- dichloroethanes, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 Mmol trifluoroacetic ethyl acetoacetate is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, is merged Organic phase is extracted with saturated ammonium chloride solution and ethyl acetate, and revolving removes organic solvent and obtains crude product, and crude product passes through silicon Plastic column chromatography obtains 4- (trifluoromethyl) pyrans simultaneously [3,4- with pentane and dichloromethane eluentb] pyrans -2,5 (6H,8H)- Diketone (separation yield 43%).1H NMR (400 MHz, CDCl3) δ 6.75 (s, 1H), 4.73 (s, 2H), 4.32 (s, 2H). 19F NMR (376 MHz, CDCl3) δ -64.5 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 186.2 (s), 173.1 (s), 156.5 (s), 140.7 (q, J = 36.4 Hz), 120.4 (q, J = 275.3 Hz), 115.6 (q, J = 7.1 Hz), 108.9 (s), 72.3 (s), 65.2 (s).
Embodiment 12
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1,3- cyclopentanedione, 1.0 mL 1,2- dichloroethanes, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 mmol trifluoroacetyl Ethyl acetate is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, merges organic phase, with full It being extracted with ammonium chloride solution and ethyl acetate, revolving removes organic solvent and obtains crude product, and crude product passes through silica gel column chromatography, with Pentane and dichloromethane eluent, obtain 4- (trifluoromethyl) -6,7- dihydro ring penta [b] pyrans -1,5- diketone (separation yield 84%)。1H NMR (400 MHz, CDCl3) δ 6.60 (s, 1H), 3.09 (t, J = 4.0 Hz, 2H), 2.79 (t, J = 4.0 Hz, 2H). 19F NMR (376 MHz, CDCl3) δ -66.3 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 194.2 (s), 187.4 (s), 158.9 (s), 139.5 (q, J = 37.2 Hz), 120.1 (q, J = 275.1 Hz), 112.7 (s), 112.6 (q, J = 6.1 Hz), 34.36 (s), 26.29 (s).
Embodiment 13
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added Phenyl -1 5-, hydroresorcinol, 1.0 mL 1,2- dichloroethanes, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 mmol tri- Acetyl fluoride ethyl acetate is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, is merged organic Phase is extracted with saturated ammonium chloride solution and ethyl acetate, and revolving removes organic solvent and obtains crude product, and crude product passes through silicagel column Chromatography, with pentane and dichloromethane eluent, obtains 7- phenyl -4- (trifluoromethyl) -7,8- dihydro -2HChromene -2,5 (6H)-diketone (separation yield 99%).1H NMR (400 MHz, CDCl3) δ 7.42 (t, J = 7.1 Hz, 2H), 7.35 (d, J = 7.0 Hz, 1H), 7.29 (d, J = 7.1 Hz, 2H), 6.71 (s, 1H), 3.55 (d, J = 5.8 Hz, 1H), 3.17 (d, J = 7.8 Hz, 2H), 3.02 – 2.60 (m, 2H). 19F NMR (376 MHz, CDCl3) δ -63.5 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 190.0 (s), 175.2 (s), 157.9 (s), 141.5 (q, J = 35.3 Hz), 140.7 (s), 129.2(s), 127.8 (s), 126.5 (s), 120.9 (q, J = 275.2 Hz), 115.3 (q, J = 7.4 Hz), 111.1 (s), 45.1 (s), 37.4 (s), 36.7 (s).
Embodiment 14
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added Phenyl -1 5-, hydroresorcinol, 1.0 mL 1,2- dichloroethanes, 0.060 mmol triethylamine, 0.45 mmol trifluoroacetyl second Acetoacetic ester is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, merges organic phase, with saturation Ammonium chloride solution and ethyl acetate extract, and revolving removes organic solvent and obtains crude product, and crude product is by silica gel column chromatography, with just Pentane and dichloromethane eluent measure 7- phenyl -4- (trifluoromethyl) -7,8- dihydro -2 using trifluomethoxybenzene as internal standardH- Chromene -2,5 (6H)-diketone fluorine composes yield 85%.Nuclear magnetic spectrogram is shown in embodiment 13.
Embodiment 15
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added Phenyl -1 5-, hydroresorcinol, 1.0 mL 1,2- dichloroethanes, 0.060 mmol pyridine, 0.45 mmol trifluoroacetyl acetic acid Ethyl ester is cooled to room temperature after being stirred to react 16 h in a closed system under the conditions of 120 DEG C of oil bath, merges organic phase, with saturation chlorine Change ammonium salt solution and ethyl acetate extracts, revolving removes organic solvent and obtains crude product, and crude product is by silica gel column chromatography, with positive penta Alkane and dichloromethane eluent measure 7- phenyl -4- (trifluoromethyl) -7,8- dihydro -2 using trifluomethoxybenzene as internal standardHBenzene And pyrans -2,5 (6H)-diketone fluorine composes yield 54%.Nuclear magnetic spectrogram is shown in embodiment 13.
Embodiment 16
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1, hydroresorcinol, 0.90 mmol ammonium acetate, 3.0 mL 1,2- dichloroethanes, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 mmol trifluoroacetic ethyl acetoacetate is cooled to room after being stirred to react 48 h in a closed system under the conditions of 140 DEG C of oil bath Temperature merges organic phase, is extracted with saturated sodium chloride solution and ethyl acetate, and revolving removes organic solvent and obtains crude product, thick to produce Object is eluted with pentane and ethyl acetate by silica gel column chromatography, obtains 4- (trifluoromethyl) -7,8- dihydroquinoline -2,5 (1H, 6H)-diketone (separation yield 78%).1H NMR (400 MHz, DMSO) δ 12.63 (br, 1H), 6.67 (s, 1H), 2.87 (t, J = 5.5 Hz, 2H), 2.48 (t, J = 6.1 Hz, 2H), 2.12 – 1.82 (dt, J = 12.0 Hz, J = 4.0 Hz, 2H). 19F NMR (376 MHz, DMSO) δ -61.2 (s, 3F). 13C NMR (101 MHz, DMSO) δ 191.6 (s), 161.5 (s), 161.0 (s), 138.6 (q, J = 33.0 Hz), 122.6 (q, J = 274.6 Hz), 119.2 (q, J = 7.0 Hz), 109.3 (s), 38.6 (s), 28.2 (s), 20.5 (s).
Embodiment 17
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 5- methyl-1, hydroresorcinol, 0.90 mmol ammonium acetate, 3.0 mL 1,2- dichloroethanes, 0.060 mmol 2- diformazan ammonia Yl pyridines, 0.45 mmol trifluoroacetic ethyl acetoacetate are stirred to react under the conditions of 140 DEG C of oil bath cold after 48 h in a closed system But to room temperature, merge organic phase, extracted with saturated sodium chloride solution and ethyl acetate, revolving removes organic solvent and slightly produced Object, crude product are eluted with pentane and ethyl acetate by silica gel column chromatography, obtain 7- methyl -4- (trifluoromethyl) -7,8- bis- Hydrogen quinoline -2,5 (1H,6H)-diketone (separation yield 91%).1H NMR (400 MHz, DMSO) δ 12.65 (br, 1H), 6.67 (s, 1H), 2.88 (d, J = 17.9 Hz, 1H), 2.64 (dd, J = 17.3, 9.3 Hz, 1H), 2.48 (d, J = 12.0 Hz, 1H), 2.28 (d, J = 10.2 Hz, 2H), 1.04 (d, J = 4.5 Hz, 3H). 19F NMR (376 MHz, DMSO) δ -61.2 (s, 3F). 13C NMR (101 MHz, DMSO) δ 191.6 (s), 161.6 (s), 160.3 (s), 138.4 (q, J = 33.0 Hz), 122.6 (q, J = 274.5 Hz), 119.1 (q, J = 7.5 Hz), 109.0 (s), 46.6 (s), 35.8 (s), 27.9 (s), 20.8 (s).
Embodiment 18
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added Phenyl -1 5-, hydroresorcinol, 1.5 mmol ammonium acetates, 3.0 mL 1,2- dichloroethanes, 0.060 mmol 2- dimethylamino Pyridine, 0.45 mmol trifluoroacetic ethyl acetoacetate are stirred to react under the conditions of 140 DEG C of oil bath cooling after 48 h in a closed system To room temperature, merging organic phase, is extracted with saturated sodium chloride solution and ethyl acetate, revolving removes organic solvent and obtains crude product, Crude product is eluted with pentane and ethyl acetate by silica gel column chromatography, obtains 4- (trifluoromethyl) -6,7- dihydro -1HRing penta [b] pyridine -2,5- diketone (separation yield 50%).1H NMR (400 MHz, DMSO) δ 13.07 (br, 1H), 6.64 (s, 1H), 2.96 (t, J = 4.0 Hz, 2H), 2.58 (t, J = 4.0 Hz, 2H). 19F NMR (376 MHz, DMSO) δ -63.9 (s, 3F). 13C NMR (101 MHz, DMSO) δ 196.5 (s), 172.3 (s), 163.0 (s), 135.5 (q, J = 34.9 Hz), 123.2 (q, J = 275.7 Hz), 117.8 (q, J = 5.6 Hz), 111.1 (s), 111.1 (s), 35.2 (s), 35.2 (s), 24.9 (s), 24.9 (s).
Embodiment 19
It under nitrogen protection atmosphere, is equipped at one in 5 mL reaction tubes of polytetrafluoroethylene (PTFE) magnetic stir bar, 0.30 mmol is added 1,3- cyclopentanedione, 1.5 mmol ammonium acetates, 3.0 mL 1,2- dichloroethanes, 0.060 mmol 2- dimethylamino naphthyridine, 0.45 mmol trifluoroacetic ethyl acetoacetate is cooled to room after being stirred to react 48 h in a closed system under the conditions of 140 DEG C of oil bath Temperature merges organic phase, is extracted with saturated sodium chloride solution and ethyl acetate, and revolving removes organic solvent and obtains crude product, thick to produce Object is eluted with pentane and ethyl acetate by silica gel column chromatography, obtains 7- phenyl -4- (trifluoromethyl) -7,8- dihydroquinoline - 2,5(1H, 6H)-diketone (separation yield 50%).1H NMR (400 MHz, DMSO) δ 12.73 (br, 1H), 7.37 (d, J = 1.5 Hz, 4H), 7.32 – 7.24 (m, 1H), 6.73 (s, 1H), 3.51 (t, J = 12.6 Hz, 1H), 3.27 – 3.15 (m, 1H), 3.03 (d, J = 17.1 Hz, 1H), 2.90 (t, J = 16.0 Hz, 1H), 2.64 (d, J = 15.1 Hz, 1H). 19F NMR (376 MHz, DMSO) δ -61.2 (s, 3F). 13C NMR (101 MHz, CDCl3) δ 190.5 (s), 161.2 (s), 159.7 (s), 142.5 (s), 138.0 (q,J = 33.3 Hz), 128.7 (s), 127.0 (s), 126.8 (s), 122.2 (q, J = 275.0 Hz), 118.9 (q, J = 6.8 Hz), 108.5 (s), 45.1 (s), 37.5 (s), 34.9 (s).
The foregoing is merely presently preferred embodiments of the present invention, all equivalent changes done according to scope of the present invention patent with repair Decorations, are all covered by the present invention.

Claims (8)

1. it is a kind of synthesize 4- trifluoromethyl -2- pyranone compounds method, it is characterised in that: with organic base small molecule be catalysis Agent, with 1, hydroresorcinol and the like and trifluoroacetic ethyl acetoacetate or ammonium acetate are raw material, in organic solvent, It reacts and 4- trifluoromethyl -2- pyranone compounds is made；The structural formula of the 4- trifluoromethyl -2- pyranone compounds are as follows:；The structural formula of the hydroresorcinol and the like are as follows:。
2. a kind of method for synthesizing 4- trifluoromethyl -2- pyranone compounds according to claim 1, it is characterised in that: The molar ratio of organic base micromolecule catalyst, hydroresorcinol and the like, trifluoroacetic ethyl acetoacetate and solvent is 0.06-0.2:0.3-1: 0.45-1.5:12.7-42。
3. a kind of method for synthesizing 4- trifluoromethyl -2- pyranone compounds according to claim 1, it is characterised in that: The organic base micromolecule catalyst is 2- dimethylamino naphthyridine, 4-dimethylaminopyridine, triethylamine, pyridine and nafoxidine Any one of；The organic solvent is 1,2- dichloroethanes, diethylene glycol dimethyl ether, dimethyl sulfoxide, N, N- dimethyl Any one of formamide, nitrobenzene, N-Methyl pyrrolidone；Described hydroresorcinol and the like is following structures Any one of formula 1- formula 7:
。
4. a kind of method for synthesizing 4- trifluoromethyl -2- pyranone compounds according to claim 1, it is characterised in that: Specific step is as follows: in nitrogen atmosphere, organic base micromolecule catalyst, 1 are added into the container with magnetic stirring apparatus, Hydroresorcinol and the like, trifluoroacetic ethyl acetoacetate and solvent, shut plug after mixing, place it in 120 It after continuing stirring at DEG C 16 hours, is filtered with 100-200 mesh silica gel, methylene chloride rinses, and merges organic phase, uses saturated ammonium chloride Solution and ethyl acetate extract, and then revolving removes organic solvent；Obtained crude product by silica gel column chromatography, with pentane and Methylene chloride is eluant, eluent, obtains 4- trifluoromethyl -2- pyranone compounds.
5. it is a kind of synthesize 4- trifluoromethyl -2- pyridinone compounds method, it is characterised in that: with organic base small molecule be catalysis Agent, with 1, hydroresorcinol and the like and trifluoroacetic ethyl acetoacetate or ammonium acetate are raw material, in organic solvent, It reacts and 4- trifluoromethyl -2- pyridinone compounds is made；The structural formula of the 4- trifluoromethyl -2- pyridinone compounds are as follows:；The structural formula of the hydroresorcinol and the like are as follows:。
6. a kind of method for synthesizing 4- trifluoromethyl -2- pyridinone compounds according to claim 5, it is characterised in that: Organic base micromolecule catalyst, hydroresorcinol and the like, trifluoroacetic ethyl acetoacetate, ammonium acetate and solvent rub You are than being 0.06-0.2:0.3-1:0.45-1.5:0.9-3:12.7-42.
7. a kind of method for synthesizing 4- trifluoromethyl -2- pyridinone compounds according to claim 5, it is characterised in that: The organic base micromolecule catalyst is 2- dimethylamino naphthyridine, 4-dimethylaminopyridine, triethylamine, pyridine and nafoxidine Any one of；The organic solvent is 1,2- dichloroethanes, diethylene glycol dimethyl ether, dimethyl sulfoxide, N, N- dimethyl Any one of formamide, nitrobenzene, N-Methyl pyrrolidone；Described hydroresorcinol and the like is following structures Any one of formula 1- formula 7:
。
8. a kind of method for synthesizing 4- trifluoromethyl -2- pyridinone compounds according to claim 5, it is characterised in that: Specific step is as follows: in nitrogen atmosphere, organic base micromolecule catalyst, 1 are added into the container with magnetic stirring apparatus, Hydroresorcinol and the like, trifluoroacetic ethyl acetoacetate, ammonium acetate and solvent, shut plug after mixing, by it It is placed at 140 DEG C after continuing stirring 48 hours, is filtered with 100-200 mesh silica gel, methylene chloride rinses, and merges organic phase, with full It is extracted with sodium chloride solution and ethyl acetate, then revolving removes organic solvent；Obtained crude product passes through silica gel column chromatography, with Pentane and ethyl acetate are eluant, eluent, obtain 4- trifluoromethyl -2- pyridinone compounds.
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